Breaking News
March 19, 2018 - AcelRx Announces Receipt of Type A FDA Meeting Minutes and Plans to Resubmit the DSUVIA New Drug Application in Q2 2018
March 19, 2018 - Eye Docs Adopt EHRs Despite Reservations
March 19, 2018 - CRISPR enhances cancer immunotherapy
March 19, 2018 - Study finds first evidence of delayed aging among Americans
March 19, 2018 - Essential oils linked to abnormal breast development in boys
March 19, 2018 - ‘Tummy Tuck’ Relieved Postpartum Back Pain/Incontinence
March 19, 2018 - New biomarkers for neuroblastoma, a type of cancer in children
March 19, 2018 - Hookah Smoking Carries a Poisoning Risk
March 19, 2018 - Do Mood and Anxiety Affect MS Disability?
March 19, 2018 - Mean depth of ultrasonographic penetration greater in autism
March 19, 2018 - Platypus milk may help combat antibiotic resistance
March 19, 2018 - U.S. IDE study of THERMOCOOL SMARTTOUCH SF Catheter completes patient enrollment
March 18, 2018 - E-cigarette use exposes adolescents to potentially cancer-causing chemicals
March 18, 2018 - GOP Senator: Solve Opioid Crisis Through Community, Not Policy
March 18, 2018 - Why is ADHD more common in boys than girls?
March 18, 2018 - Measles alert after two passengers with the disease fly into US
March 18, 2018 - FDA looks to remove nicotine from cigarettes
March 18, 2018 - FDA moves to cut nicotine in cigarettes, helping smokers kick habit
March 18, 2018 - Athenex Announces Phase II Clinical Study Results for KX2-391 Ointment for the Treatment of Actinic Keratosis
March 18, 2018 - Surgery Tied to Better Outcomes in Kids with T2D
March 18, 2018 - Scientists use nanotechnology to detect molecular biomarker for osteoarthritis
March 18, 2018 - Research establishes use of chimeric cells as potential therapy for Duchenne muscular dystrophy
March 18, 2018 - Researcher working to develop improved endoscopic probe for colonoscopies
March 18, 2018 - Researchers develop way to sequence entire fetal genome by modifying prenatal testing method
March 18, 2018 - FDA Approves PDUFA Fee Waiver for Gimoti New Drug Application
March 18, 2018 - P2Y12 Tx Subsidy Yields Positive Response from Docs, Patients
March 18, 2018 - Are Proteins in Formula Linked to Type 1 Diabetes?
March 18, 2018 - Exercise does not seem to increase bone marrow edema in healthy people
March 18, 2018 - Researchers delineate architecture of nuclear pore complex in yeast cells
March 18, 2018 - ‘It’s Just Ghetto-izing People’: What We Heard This Week
March 18, 2018 - Alzheimer’s disease: Neuronal loss very limited
March 18, 2018 - Study reveals impact of intense, changing work schedules experienced by medical interns
March 18, 2018 - Jobs That Keep the Mind Sharp … Even Into Retirement
March 18, 2018 - Facial Scarring Improved with Botulinum Toxin
March 18, 2018 - Data detectives shift suspicions in Alzheimer’s to inside villain
March 18, 2018 - Shorter Preventive TB Tx Effective for HIV+ Patients
March 18, 2018 - New technique for identifying alcoholism puts treatment options at patients’ and providers’ fingertips
March 18, 2018 - Researchers uncover four microRNAs as potential biomarkers for atrial fibrillation
March 18, 2018 - IRX Therapeutics Announces Initiation of Phase 2 Clinical Trial of IRX-2 in Squamous Cervical or Vulvar Intraepithelial Neoplasia 3
March 18, 2018 - OncoBreak: Learning from Silence; ‘Rigged’ Drug System; NCCN Guidelines Questioned
March 18, 2018 - The coffee cannabis connection
March 18, 2018 - Novel centrifugal-flow pump for heart failure patients provides improved long-term outcomes
March 18, 2018 - U.S. FDA Accepts New Drug Application for Prucalopride (SHP555) for Chronic Idiopathic Constipation
March 18, 2018 - Cath Lab Recap: iFR vs FFR $$; Ridaforolimus-Eluting Stent
March 18, 2018 - Tree care workers need better training to handle dangers on the job, study finds
March 18, 2018 - Dementia patients do not undergo diagnostic evaluation at onset of disease, study finds
March 18, 2018 - Transplanting enhanced interneurons restores brain rhythms in mouse model of Alzheimer’s
March 18, 2018 - Gene Therapy Flops for Critical Limb Ischemia
March 17, 2018 - Study spotlights risks in anesthesiologist handoffs
March 17, 2018 - Verb fluency test may be useful tool for differential diagnosis of cognitive failure
March 17, 2018 - Health Tip: Suggestions to Improve Your Cholesterol
March 17, 2018 - Fructans Suspect in Non-Celiac Gluten Sensitivity
March 17, 2018 - Aspirin therapy appears safe before thyroid surgery
March 17, 2018 - Minimally invasive surgical device may one day provide lasting heart repair
March 17, 2018 - UIH and RaySearch enter into new partnership
March 17, 2018 - Is BMI Too Inexact? | Medpage Today
March 17, 2018 - Sleep apnea study finds male-female differences in cerebral cortex thickness, symptoms
March 17, 2018 - Leicester research could help identify people with asthma of different severities
March 17, 2018 - Biosense Webster enrolls and treats first AF patient in clinical study of new RF balloon catheter
March 17, 2018 - Participants in rogue herpes vaccine research take legal action
March 17, 2018 - Imara Doses First Patient in Phase 2a Clinical Trial of IMR-687 for Sickle Cell Disease
March 17, 2018 - AAP: Prevent Medication Errors by Improving Processes
March 17, 2018 - Severe sleep apnea during REM sleep tied to acute CV events
March 17, 2018 - Alzheimer’s disease also affects small blood vessels
March 17, 2018 - Jazz Pharmaceuticals Announces FDA Acceptance of NDA for Solriamfetol (JZP-110) for Excessive Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea
March 17, 2018 - Switching Biologics in Psoriasis Care
March 17, 2018 - Polygenic risk score may identify alzheimer’s risk in younger populations
March 17, 2018 - Genetic heart mutations account for fewer sudden and unexplained infant deaths
March 17, 2018 - Clinical trial to test efficacy of stem cell transplants in stopping ALS muscle deterioration
March 17, 2018 - Researchers team up to improve life for children with microcephaly
March 17, 2018 - Health guide for young women regarding labiaplasty
March 17, 2018 - Inhaled Nitrite Flops as HFpEF Therapy
March 17, 2018 - California mental health tax providing services to needy in L.A. County, study finds
March 17, 2018 - Cancer survivors become fatigued more quickly than their peers, study finds
March 17, 2018 - Study finds common presence of nightmares among U.S. military personnel
March 17, 2018 - Yellow fever outbreak in Brazil necessitates vaccination for travelers
March 17, 2018 - Health Tip: Waist Size May Help Predict Heart Attack
March 17, 2018 - Low-Dose Combo Pill Successfully Takes Down High BP
March 17, 2018 - Most children with sickle cell anemia not receiving key medication to stay healthy
March 17, 2018 - YCC launches new Yale Center for Immuno-Oncology
Antigen study supports new approach to vaccine for respiratory syncytial virus

Antigen study supports new approach to vaccine for respiratory syncytial virus

image_pdfDownload PDFimage_print
Immune system antibodies can block RSV infection and provide protection from RSV disease. This image shows how a protective human antibody (dark and light grey surface) sticks to a folded part of the RSV G protein antigen (rainbow colored blue-to-red). The new findings provide a foundation for the development of a RSV vaccine. Credit: Rebecca DuBois

Medical researchers have been trying to develop a vaccine for respiratory syncytial virus (RSV) for more than 50 years, without success. New findings by researchers at UC Santa Cruz, however, point to a promising route for designing an effective vaccine.

For most people, an RSV infection is just a bad cold, but for infants and older adults it can cause serious pneumonia or bronchial inflammation. In the 1960s, a traditional vaccine based on inactivated virus was found to actually make the disease worse. More recently, clinical trials of two different vaccines based on one of the viral surface proteins (the RSV F glycoprotein) have also failed.

The new study, published March 9 in Science Immunology, focused on the other major viral surface protein, the RSV G glycoprotein. Leveraging work by collaborators at Trellis Bioscience who have isolated protective human antibodies targeting the G glycoprotein, the UCSC researchers determined the atomic structure of RSV G and identified two sites on it that are targeted by protective antibodies effective against a broad range of RSV strains.

Corresponding author Rebecca DuBois, assistant professor of biomolecular engineering at UC Santa Cruz, said RSV G had been overlooked by vaccine researchers because initial studies found that deleting the gene for it didn’t stop the virus from replicating in cell cultures. Studies in animal models, however, showed that virus lacking the G glycoprotein is significantly weakened.

Crystal structures of protein complexes formed between RSV G antigen (cyan) and broadly neutralizing monoclonal antibody 3D3 (light and dark grey). Credit: Fedechkin et al., Sci. Immunol. 3, eaar3534 (2018)

“The G glycoprotein is actually very important,” DuBois said. “It’s the attachment protein that allows the virus to stick to lung cells, while the F glycoprotein promotes entry into the cell. Once the virus infects a cell and starts replicating, it makes a secreted form of the G glycoprotein that goes out and starts flipping switches on our immune cells, distorting our immune responses.”

This disruption of the immune response by RSV G may explain why vaccines based on RSV F have failed, she said. “You need a protective antibody response that blocks that RSV G activity, but we didn’t know how antibodies target RSV G at the molecular level.”

In the new study, DuBois showed that these protective antibodies target a section of the protein called the central conserved domain that is the same in all strains of the virus. The researchers determined the three-dimensional atomic structures of the precise binding sites of two Trellis antibodies—crucial information for designing a vaccine that can induce the immune system to produce such protective antibodies.

Video interview (with music overlay) with corresponding author Rebecca Dubois, who talks about the inspiration behind her research of a respiratory syncytial virus vaccine and the implications of her findings. Credit: Credit: Andrew Jones / UC Santa Cruz

“We’re really excited about the possibility of finally being able to conquer this virus, which is one of the most important childhood viruses for which we don’t have a vaccine,” DuBois said.

In developing a vaccine based on RSV G, however, researchers would have to ensure that the vaccine lacks the viral protein’s ability to disrupt the immune system. “There has been a lot of concern about making a vaccine with the G glycoprotein. We need to engineer it so that it can’t subvert the immune system, while keeping its ability to elicit an effective antibody response,” DuBois said.

Trellis Bioscience, meanwhile, is investigating the therapeutic use of the antibodies themselves to treat infants with RSV infection and severe lung congestion, with clinical trials expected to start in early 2019. If proven effective, the demand for a vaccine that elicits protective antibodies targeting the G glycoprotein will intensify, particularly for global use, DuBois said.

Explore further:
Why the latest shingles vaccine is more than 90 percent effective

More information:
S.O. Fedechkin el al., “Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies,” Science Immunology (2018). … 6/sciimmunol.aar3534

Journal reference:
Science Immunology

Provided by:
University of California – Santa Cruz

Tagged with:

About author

Related Articles